Consortium

VHIO is a leading non for profit research organization where its scientists and physicians adopt a purely translational approach (“forward and reverse”) to research in order to realize personalized medicine by turning research into more effective targeted treatments and better practice for the care of our patients, in a multidisciplinary setting. Research is linked with various research areas carried out by other VHIO groups, connecting molecular biology and the best tumour models with pharmacology and innovative clinical research. Our scientists are collaborating closely in trials to facilitate biomarker development as well as research in mechanisms of cancer development.

The Institute has a broad expertise in carrying out clinical trials with pathway targeted inhibitors and studies for the development of novel diagnostic/prognostic tools and translational research. VHIO is part of the Vall d’Hebron University Hospital Complex, and performs translational and early clinical research providing a link between basic and clinical research at the Hospital.

The Medical Oncology Department of the Vall d’Hebron Hospital has an outstanding Clinical Research Program integrated by more than 30 staff medical oncologists, in addition to research fellows, clinical study coordinators, clinical study assistants, research nurses and clinical pharmacists. In 2013, the Centre conducted 232 clinical trials in solid tumours and 75 phase I clinical trials with novel targeted agents, and a total of 843 patients participated in therapeutic trials (345 in phase I trials).

Role in MoTriColor

VHIO is involved in the development of all the WPs of the MoTriColor project as coordinator of the present proposal, having a key role in the clinical research activities, leading WP4 and being involved in WPs 2 and 3. VHIO’s research is performed in a multidisciplinary way, involving medical oncologists, surgeons, pathologists, basic/translational researchers and bioinformaticians, among other professionals.

As project coordinator, VHIO also leads WPs 8 and 9, related to project coordination and management and the dissemination activities. VHIO´s Scientific Coordination Area is a core instrument of our Institute performing important supportive functions, including all those related to project management, legal advice, technology transfer, and contracts negotiation. VHIO also counts with a Communication Department that will lead the dissemination activities through different media: MoTriColor logo and webpage, newsletter, newspapers, appearance in magazines, etc.

Catalan Institute of Oncology (ICO) is a comprehensive cancer centre devoted to minimize the cancer impact. Research is part of ICO’s main objectives, as stated in its foundational statutes. ICO’s main goals are conduction, management and delivering of services to cancer patients, in the fields of care, education and research, as well as designing and implementing studies and actions regarding cancer epidemiology and control. ICO has 1,000 workers (77,2 % women), 130 of whom are exclusively devoted to cancer research. It was established in 1995 by the Health Department of the Catalan Government, and started operations one year later at the facilities of the Duran i Reynals Hospital in Hospitalet de Llobregat, Barcelona. Since then, two more branches have been opened in Girona and Badalona.

The colon cancer research group at ICO is a clinical and translational group led by Dr. Ramon Salazar, a clinical oncologist with a highstanding profile in translational research, leading the colon cancer clinics at all ICO sites (L’Hospitalet, Badalona, Girona and Moises Broggi). The translational laboratory at ICO is currently holding six outstanding research groups, one of them, the virotherapy and immunology, led by Dr. Ramon Alemany with a more than 20 years’ experience in the field. The translational laboratory is directed by Dr. Salazar as a sign of the tight relationship between the clinical practice and the translational research at ICO.

The Cancer Prevention and Control Program at ICO, led by Dr. Victor Moreno runs the population-based breast and colorectal cancer screening programs within the area of L’Hospitalet (Barcelona). The research within this Program is focused on cancer prevention, genetic epidemiology, molecular diagnosis of cancer, biomarkers of diagnosis, prognosis and prediction of therapeutic response, and the identification of new preventive or therapeutic targets. The team is multidisciplinary with epidemiologists, biologists, bioinformatics, biostatisticians, nurses, and documentalists.

Role in MoTriColor

ICO is leading WP5 and WP6, but also provides study subjects and will contribute to the creation of a database that compiles clinical, epidemiological, and genetic information of such patients. In collaboration with other partners, ICO helps identifying project products susceptible of IP protection and commercial exploitation, and ensures that the project has proper impact in the scientific community and society through dissemination activities.

Agendia is at the forefront of developing personalized medicine, striving to develop more effective, individualized treatments within reach of cancer patients. Building on a well-established genomics platform for tumor gene expression profiling, the company’s tests help physicians more accurately tailor cancer treatments. Agendia currently markets three commercial breast cancer tests. Agendia’s flagship product, MammaPrint, was the first multi-gene diagnostic test to receive FDA clearance in 2007. . In addition, Agendia collaborates with pharmaceutical companies to develop companion diagnostic tests in the area of oncology. Agendia’s corporate headquarters and 1st commercial genomics laboratory is located in Amsterdam, The Netherlands. In 2009, Agendia opened its 2nd CLIA and CAP certified and compliant genomics laboratory in California – now located in Irvine – to augment its testing capacity within the USA.

Role in MoTriColor

Agendia has developed and validated three gene signatures in an EU FP7 project (COLTHERES) on colorectal cancer. These signatures will now be utilized and validated in prospective clinical setting in the current HORIZON 2020 project by selecting for patients to benefit from specific colorectal cancer therapies.

The Netherlands Cancer Institute (Stichting Het Nederlands Kanker Instituut – NKI) is an independent research institute focusing on all aspects of cancer research. The NKI works closely together with the Antoni van Leeuwenhoek hospital (AVL), which provides care and treatment for cancer patients. Together they form a Comprehensive Cancer Centre (OECI accredited). The close interaction between the NKI and the AVL ensures rapid translation of basic finding to new clinical applications.

The NKI employs approximately 650 scientists. It has 50 principal investigators (faculty, group leaders) in basic and translational research. The AVL is a 180 bed specialized cancer hospital and has approximately 55 clinicians that are involved in translational research projects and/or clinical trials. The NKI has approximately 180 Postdoctoral fellows, 190 PhD students and 180 technicians. PIs, postdocs, PhD students and technicians are from the Netherlands but more and more of our researchers come from abroad (at this moment 35%).

The research at the Netherlands Cancer Institute covers all aspects of cancer research, from basic research, via translational research to clinical trials (the latter performed in collaboration with the AVL). We have a strong basic and translational research activity in the areas of (micro)biology, biochemistry, genetics and immunology. Furthermore our department of psychosocial research investigates the position of cancer patients and their relatives within society and how they cope with their disease.

Researchers at NKI can use all research facilities offered by the Institute, mostly for free. The Institute has an extensive mouse facility with special units for transgenesis, cryopreservation, pathology and a mouse cancer clinic. Furthermore, there are facilities for (deep) sequencing, robotics, statistics, protein expression and purification, peptide synthesis, biochemical characterization of proteins, mass spec analysis, flow cytometry, digital microscopy, electron microscopy and screenings facilities using small molecule and biological reagent libraries, including large scale loss of function genetic screens using shRNA and CRISPR libraries. Most facilities have dedicated staff that will help the researchers plan and perform their experiments. The facilities have state-of-the-art equipment.

To facilitate translational and clinical research, dedicated support is provided for clinical trials and for the use of patient data and materials.

The NKI offers an open, collaborative, but critical surrounding in which scientific excellence is stimulated. The open atmosphere makes that scientist within the Institute help each other with reagents, ideas and critical comments. This has resulted in international recognition of the NKI as one of the best places for cancer research.

Role in MoTriColor

Prof. Jan Schellens is a medical oncologists who has led many early phase clinical trials for cancer over two decades. He uses his very well organised early phase clinical trial unit to lead two clinical trials of the consortium.

The EORTC is a non-profit international research organisation created under Belgian law in 1962. Since its creation, the EORTC has contributed to improve the survival rates for several types of cancer through translational and clinical research. Over than 30 EORTC sponsored clinical trials are open to patient recruitment at any given time. Both multinational and multidisciplinary, the EORTC Network comprises more than 2,000 collaborators from all disciplines involved in cancer treatment and research in more than 300 university hospitals in over 30 countries. EORTC databases contain quality assured data from some 180,000 cancer patients from EORTC clinical trials. Currently, some 50,000 patients are being followed-up after treatment. The scientific activities of EORTC are strictly peer-reviewed and subject to quality assurance/ quality control programs. The EORTC operates on an independent basis, and in this capacity is able to work in partnership with the pharmaceutical industry in evaluating innovative molecules. EORTC has contributed to several success stories in terms of new anti-cancer drugs development including registrations by the FDA and the EMA. The EORTC has proven track records in establishing new standards e.g. Response Evaluation Criteria In Solid Tumours (RECIST), quality of life of cancer patients, etc. The EORTC has recently launched the SPECTA program involving molecular screening platforms for efficient biomarkers driven clinical trials access in lung, colorectal, melanoma, prostate and brain cancers.

Role in MoTriColor

The EORTC is a pan European clinical and translational clinical research infrastructure which has integrated in its scientific strategy and its operational set ups solutions to address the challenges of modern oncology and notably conducting and developing new forms of clinical research for personalized medicine. Therefore, EORTC has the capacity to operationalise research projects with the aims of qualifying, validating and demonstrating the clinical utility of new biomarkers for molecularly defined sub group of patients. The infrastructure applies the highest standards of quality assurance and quality control to ensure regulatory acceptance of targets and clinical trials outcomes.

Grande Ospedale Metropolitano Niguarda, in brief Ospedale Niguarda, is one of the biggest general hospitals in Italy, national and international reference center for virtually for all diseases and therapeutic areas, with a dedication to excellence and multidisciplinary care. It houses all the clinical specialties for pathologies of adults and children delivered through 74 Clinical Units, arranged in 11 Clinical Departments, and 4 Centers. More than 4100 employees comprise 750 physicians and more than 2.000 nurses, health technicians, physical therapists, and obstetric nurses. There are 70 buildings for hospitalized patients and more than 200 clinics. Every year Niguarda offers over 2.500.000 ambulatory visits and over 40.000 admissions. Among its clinical units, Niguarda includes 26 units which are reference point in Italy for their recognized specialties: cell factory, anti-poison centre, regional emergency centre (city emergency plan headquarter), trauma burn centre, equestrian rehabilitation centre, rare diseases unit (over 100 treated diseases), surgery. The 4 multidisciplinary Centers (Niguarda Cancer Center, Niguarda Transplant Center Niguarda Trauma Ceter and Niguarda Cardiovascular Center) have the task of coordinating care, clinical research and knowledge sharing. In particular, the Falck Division of Oncology of the Niguarda Cancer Centre is a centre for phase I-III clinical trials and performed studies leading to regulatory labeling recognition of several targeted agents which have been paralleled by fulfillment of FDA and AIFA (Agenzia Italiana Farmaco) inspections.

The Falck Division of Oncology, integrated in the Niguarda Cancer Center, will be involved in the present project in virtue of its expertise in investigational clinical care for the treatment of solid tumors, especially gastrointestinal mainly collorectal, lung, breast, ovarian and uterine cancers, and sarcomas, medulloblastomas, germ cell, neuroendocrine tumors and carcinomas of unknown primary site. It is a teaching site for the School of Medicine and the School of Oncology of Università degli Studi di Milano.

Role in MoTriColor

The Falck Division of Oncology possesses sufficient experience and facilities to fulfil the tasks of present study. The clinical research carried out in the last 5 years in the field of targeted therapy of colorectal cancer (CRC) has represented the platform for the design and implementation of several grant proposals (see next section). In particular, clinical facilities for medical oncology, new drug clinical development, molecular oncology and diagnostics as well as appropriate logistics are already in place with success and scientific productivity. Moreover, in collaboration with the Divisions of Surgery, Pathology, Interventional Radiology and Endoscopy, CRC represents one of the major areas of research with an ongoing high quality scientific production and several doctoral MD theses.

The Foundation for the Research of the University Clinic Hospital of Valencia (INCLIVA) was constituted in the year 2000 and is a top 10 biomedical research institute in Spain. It is organized around four priority areas of research: cardiovascular, oncology, metabolism and organic damage and reproductive medicine. INCLIVA (www.incliva.es) is included in the framework of centres of scientific excellence promoted by the Spanish Ministry of Economy and Competitiveness, and in 2011 it was accredited by the National Health Institute Carlos III as an Institute of Research in Health Sciences. INCLIVA is the institution managing the research in Health of the University Clinic Hospital (that includes a Department providing healthcare to 350.000 inhabitants all of them with a EHR), the University of Valencia and the Valencian Infertility Institute (IUIVI). INCLIVA has participated in several research projects funded by the European Commission such as EU-MASCARA, INGENIOUS HyperCare, EPICHEM or C-POC among others.

The Research Group on Colorectal Cancer and New Therapeutic Developments in Solid Tumours led by Professor Andres Cervantes has as the main strategic aims to facilitate precision medicine with innovative therapeutic approaches particularly in gastrointestinal cancers to improve on the molecular classification and predictive biomarkers. Their lines of research also include the development of liquid biopsies for early diagnosis, monitoring and predicting therapeutic effects.

Role in MoTriColor

Main tasks attributed to INCLIVA are those related to the definition of molecular alterations and the main characteristics of the colorectal cancer from the recruited patients. As previous experience related to those tasks, INCLIVA by means of Dr. Cervantes and together with the Medical Central Research Unit has implemented the detection of 256 mutations on 19 oncogenes using the Sequenom Platform. His group has also large experience in defining experimental therapies based on the molecular characteristics of patients.

The Division of Medical Oncology is within the Dipartimento Medico-Chirurgico di Internistica Clinica e Sperimentale “F. Magrassi e A. Lanzara” (University Department) in the Seconda Università degli studi di Napoli (SUN). The participant is Full Professor of Medical Oncology, Head of the Division and Director of the University Department. The research unit is composed of the participant and of three senior researchers (see below for details). There are approximately 10 trainees, such as residents in Medical Oncology, doctoral and post-doctoral fellows that are also fully time actively involved in the research programs of this Unit under the direct supervision of the three senior researchers.

Role in MoTriColor

The research unit has a long term commitment and experience in translational research in the area of the proposal. The participant and his group have developed an internationally recognized expertise in the preclinical and clinical development of therapeutic strategies against the epidermal growth factor receptor (EGFR) pathway in solid tumors, in particular in colorectal and lung cancers. A major research interest is the study of the mechanisms of intrinsic and acquired resistance to EGFR inhibitors in such cancers and, in particular, the study of the cell membrane growth factor receptor activated RAS-RAF-MEK-ERK intracellular signalling in cancer cells. The aim of this research program is the development of more effective and personalized molecular targeted therapies in cancer by a better molecular characterization of the tumor in the individual patient with the most appropriate and rational selection of molecular targeted drugs alone, in combination or in sequence.

The Dept. of Oncology of the University of Torino, School of Medicine is located at the Candiolo Cancer Research Institute, in Candiolo, Italy. The Department encompasses experimental and clinical researchers and aims at making significant contribution to the fight against cancer by understanding the basics and by providing optimal diagnostic and therapeutic services. The Institute employ over 300 hundreds scientists and is a recognized and well-qualified centre for training young researchers in the experimental medical science field. The equipment include: Sterile room, with laminar flow hoods biohazard II and CO2 incubators; -Light and fluoresce microscopes with a CCD camera and interactive systems for cell biology and molecular cytogenetic analyses; -FACS analysis and cell sorting -Confocal microscopy; -Geneamp PCR system 9700 termocycler; -ViiA7 Real Time-PCR system (Applied Biosystems) equipped with adaptor for 384-samples microfluidic cards; -96-well microplates reader (Tecan); -General laboratory equipment (centrifuges, microfuges, apparatus for protein and nucleic acid electrophoresis, cold room at 4°C, freezers -20 and -80); DNA sequencing (see below for further details, microsatellite analysis, microarray Agilent platforms; -Microbiology; -Dedicated rooms for the manipulation of biohazard level III MOGMs; – Micro-PET -Facilities for Animal housing (nude, NOD/SCID, mice of various strains) with centralized food and cage-washing services. Animals are housed in ventilated racks and subjected to 12 hour light/dark cycles. Basic husbandry is provided by certified technical staff.

Role in MoTriColor

The group of Alberto Bardelli has developed innovative approaches to detect cancer alleles in the blood of patients (see publications). His group has identified mechanisms of acquired resistance to targeted therapies by analyses of circulating tumour DNA. For example he defined the role of KRAS, BRAF and NRAS mutation and HER2 and MET amplification in resistance to EGFR blockade in CRCs. Within the frame of MoTriColor Dr. Bardelli’s group will identify patient’s specific genotypes and track them over the course of the clinical trials. His group will also longitudinally follow response of patients during therapy treatment and help defining the molecular bases of relapse.

Katholieke Universiteit Leuven (KU Leuven) boasts a rich tradition of education and research that dates back six centuries. KU Leuven is currently by far the largest university in Belgium in terms of research funding and expenditure (EUR 365 million in 2012), and is a charter member of LERU. Leuven participates in over 540 highly competitive European research projects (FP7, 2007-2013), ranking sixth in the leage of HES institutions participating in FP7. KU Leuven takes up the 8th place of European institutions hosting ERC grants. The success in the FP7 Marie Curie Actions is a manifestation of the three pillars of KU Leuven: research, education and service to society with 136 actions. KU Leuven employs 7,018 researchers on its academic staff (2013). KU Leuven is consistently considered to be within the top 100 universities of the world.

UZ Leuven (Universitair Ziekenhuis Leuven) is the teaching hospital associated with the KU Leuven. UZ Leuven has been offering medical care at the highest standards of quality and innovation for more than 75 years. The hospital has 4 campuses: Gasthuisberg, Pellenberg, Sint-Pieter and Sint-Rafaël. With 1995 beds and over 8.800 staff members, UZ Leuven is one of the largest hospitals in Belgium. The strength of UZ lies in the combination of research, training and pluri-disciplinary patient care, that is subject to continuous critical reflection and evaluation.

Role in MoTriColor

The profile of the Investigator is dual: Research and Clinical management of colorectal cancer. Based on the Clinical activities, the researcher and Institution match the call by their international leadership in trials in colorectal cancer, involvement in most Phase III trials in the disease, often as lead institute and their high clinical turnover of colorectal cancer patients to be screened for MoTriColor and their expertise and infrastructure for early phase clinical trials and translational research. From the research perspective the investigator has been intimately linked to the development of colorectal cancer subtypes utilized in this project, leading the international consensus effort in this field and generate a lot of the data that serve to build this proposal. Investigator is also a board member and of the EORTC and PI of a clinical trials platform for colorectal cancer, facilitating the molecular screening of CRC pts in multiple European institutions for inclusion in molecularly targeted trials.